Further evidence that endorphins figure importantly in pain
control comes from a new look at some of the oldest and newest
pain treatments. The new look frequently involves the use of a
drug that prevents endorphins and morphine from working.
Injections of this drug, naloxone, can result in a return of pain
which had been relieved by morphine and certain other treatments.
But, interestingly, some pain treatments are not affected by
naloxone: Their success in controlling pain apparently does not
depend on endorphins. Thus nature has provided us with more than
one means of achieving pain relief.

Acupuncture. Probably no therapy for pain has stirred
more controversy in recent years than acupuncture, the
2,000-year-old Chinese technique of inserting fine needles under
the skin at selected points in the body.
The needles are
agitated by the practitioner to produce pain relief which some
individuals report lasts for hours, or even days. Does
acupuncture really work? Opinion is divided. Many specialists
agree that patients report benefit when the needles are placed
near where it hurts, not at the body points indicated on
traditional Chinese acupuncture charts. The case for acupuncture
has been made by investigators who argue that local needling of
the skin excites endorphin systems of pain control. Wiring the
needles to stimulate nerve endings electrically
(electroacupuncture) also activates endorphin systems, they
believe. Further, some experiments have shown that there are
higher levels of endorphins in cerebrospinal fluid following
acupuncture.

Those same investigators note that naloxone injections can
block pain relief produced by acupuncture. Others have not been
able to repeat those findings. Skeptics also cite long-term
studies of chronic pain patients that showed no lasting benefit
from acupuncture treatments. Current opinion is that more
controlled trials are needed to define which pain conditions
might be helped by acupuncture and which patients are most likely
to benefit.

Local electrical stimulation. Applying brief pulses of
electricity to nerve endings under the skin, a procedure called
transcutaneous electrical nerve stimulation (TENS), yields
excellent pain relief in some chronic pain patients. The
stimulation works best when applied to the skin near where the
pain is felt and where other sensibilities like touch or pressure
have not been damaged. Both the frequency and voltage of the
electrical stimulation are important in obtaining pain relief.

Brain stimulation. Another electrical method for
controlling pain, especially the widespread and severe pain of
advanced cancer, is through surgically implanted electrodes in
the brain. The patient determines when and how much stimulation
is needed by operating an external transmitter that beams
electronic signals to a receiver under the skin that is connected
to the electrodes. The brain sites where the electrodes are
placed are areas known to be rich in opiate receptors and in
endorphin-containing cells or fibers. Stimulation-produced
analgesia (SPA) is a costly procedure that involves the risk of
brain surgery. However, patients who have used this technique
report that their pain "seems to melt away." The pain relief is
also remarkably specific: The other senses remain intact, and
there is no mental confusion or cloudiness as with opiate drugs.
NINDS is currently supporting research on how SPA works and is
also investigating problems of tolerance: Pain may return after
repeated stimulation.

Placebo effects. For years doctors have known that a
harmless sugar pill or an injection of salt water can make many a
patient feel better -- even after major surgery. The placebo
effect, as it has been called, has been thought to be due to
suggestion, distraction, the patient's optimism that something is
being done, or the desire to please the doctor (placebo means "I
will please" in Latin).

Now experiments suggest that the placebo effect may be
neurochemical, and that people who respond to a placebo for pain
relief -- a remarkably consistent 35 percent in any experiment using
placebos -- are able to tap into their brains' endorphin systems.
To evaluate it, two NINDS- and NIDR-supported investigators at
the University of California at San Francisco designed an
ingenious experiment. They asked adults scheduled for wisdom
teeth removal to volunteer in a pain experiment. Following
surgery, some patients were given morphine, some naloxone, and
some a placebo. As expected, about a third of those given the
placebo reported pain relief. The investigators then gave these
people naloxone. All reported a return of pain.

How people who benefit from placebos gain access to pain
control systems in the brain is not known. Scientists cannot
even predict whether someone who responds to a placebo in one
situation will respond in another. The San Francisco
investigators suspect that stress may be a factor. Patients who
are very anxious or under stress are more likely to react to a
placebo for pain than those who are more calm, cool, and
collected. But dental surgery itself may be sufficiently
stressful to trigger the release of endorphins -- with or without
the effects of placebo. For that reason, many specialists
believe further studies are indicated to analyze the placebo
effect.

As research continues to reveal the role of endorphins in
the brain, neuroscientists have been able to draw more detailed
brain maps of the areas and pathways important in pain perception
and control. They have even found new members of the endorphin
family: Dynorphin, the newest endorphin, is reported to be 10
times more potent a painkiller than morphine.

At the same time, clinical investigators have tested chronic
pain patients and found that they often have lower-than-normal
levels of endorphins in their spinal fluid. If you could just
boost their stores with man-made endorphins, perhaps the problems
of chronic pain patients could be solved.

Not so easy. Some endorphins are quickly broken down after
release from nerve cells. Other endorphins are longer lasting,
but there are problems in manufacturing the compounds in quantity
and getting them into the right places in the brain or spinal
cord. In a few promising studies, clinical investigators have
injected an endorphin called beta-endorphin under the membranes
surrounding the spinal cord. Patients reported excellent pain
relief lasting for many hours. Morphine compounds injected in
the same area are similarly effective in producing long-lasting
pain relief.

But spinal cord injections or other techniques designed to
raise the level of endorphins circulating in the brain require
surgery and hospitalization. And even if less,drastic means of
getting endorphins into the nervous system could be found, they
are probably not the ideal answer to chronic pain. Endorphins
are also involved in other nervous system activities such as
controlling blood flow. Increasing the amount of endorphins
might have undesirable effects on these other body activities.
Endorphins also appear to share with morphine a potential for
addiction or tolerance.

Meanwhile, chemists are synthesizing new analgesics and
discovering painkilling virtues in drugs not normally prescribed
for pain. Much of the drug research is aimed at developing
nonnarcotic painkillers. The motivation for the research is not
only to avoid introducing potentially addictive drugs on the
market, but is based on the observation that narcotic drugs are
simply not effective in treating a variety of chronic pain
conditions. Developments in nondrug treatments are also
progressing, ranging from new surgical techniques to physical and
psychological therapies like exercise, hypnosis, and biofeedback.

This article was provided by U.S. National Institutes of Health.
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